Skeletal muscles can be voluntarily controlled, under normal circumstances. Skeletal muscles that cramp the most often are the calves, thighs, and arches of the foot, and are sometimes called a "Charley horse" or a "corky". Such cramping is associated with strenuous physical activity and can be intensely painful; however, they can even occur while inactive and relaxed. Around 40% of people who experience skeletal cramps are likely to endure extreme muscle pain, and may be unable to use the entire limb that contains the "locked-up" muscle group. It may take up to seven days for the muscle to return to a pain-free state.

Nocturnal leg cramps are involuntary muscle contractions that occur in the calves, soles of the feet, or other muscles in the body during the night or (less commonly) while resting.

The duration of nocturnal leg cramps is variable, with cramps lasting anywhere from a few seconds to several minutes. Muscle soreness may remain after the cramp itself ends. These cramps are more common in older people.[5] They happen quite frequently in teenagers and in some people while exercising at night. The precise cause of these cramps is unclear. Potential contributing factors include dehydration, low levels of certain minerals (magnesium, potassium, calcium, and sodium, although the evidence has been mixed),[6][7][8] and reduced blood flow through muscles attendant in prolonged sitting or lying down. Nocturnal leg cramps (almost exclusively calf cramps) are considered "normal" during the late stages of pregnancy.[citation needed] They can, however, vary in intensity from mild to extremely painful.

A lactic acid buildup around muscles can trigger cramps; however, these happen during anaerobic respiration when a person is exercising or engaging in an activity where the heartbeat speeds up. Medical conditions associated with leg cramps are cardiovascular disease, hemodialysis, cirrhosis, pregnancy, and lumbar canal stenosis. Differential diagnoses include restless legs syndrome, claudication, myositis, peripheral neuropathy. All of these can be differentiated through careful history and physical examination.[8]

Gentle stretching and massage, putting some pressure on the affected leg by walking or standing, or taking a warm bath or shower may help to end the cramp.[9] If the cramp is in the calf muscle, pulling the big toe gently backwards will stretch the muscle and, in some cases, cause almost immediate relief. There is limited evidence supporting the use of magnesium, calcium channel blockers, carisoprodol, and vitamin B12.[8]

Besides being painful, a nocturnal leg cramp can cause much distress and anxiety.[11]Statins may sometimes cause myalgia and cramps among other possible side effects. Raloxifene (Evista) is a medication associated with a high incidence of leg cramps. Additional factors, which increase the probability for these side effects, are physical exercise, age, female gender, history of cramps, and hypothyroidism. Up to 80% of athletes using statins suffer significant adverse muscular effects, including cramps;[12] the rate appears to be approximately 10–25% in a typical statin-using population.[13][14] In some cases, adverse effects disappear after switching to a different statin; however, they should not be ignored if they persist, as they can, in rare cases, develop into more serious problems. Coenzyme Q10 supplementation can be helpful to avoid some statin-related adverse effects, but currently there is not enough evidence to prove the effectiveness in avoiding myopathy or myalgia.[15]

Skeletal muscles work as antagonistic pairs. Contracting one skeletal muscle requires the relaxation of the opposing muscle in the pair. Cramps can occur when muscles are unable to relax properly due to myosin fibers not fully detaching from actin filaments. In skeletal muscle, adenosine triphosphate (ATP) must attach to the myosin heads for them to disassociate from the actin and allow relaxation; the absence of ATP in sufficient quantities means that the myosin heads remains attached to actin. An attempt to force a muscle cramped in this way to extend (by contracting the opposing muscle) can tear muscle tissue and worsen the pain. The muscle must be allowed to recover (resynthesize ATP), before the myosin fibres can detach and allow the muscle to relax.

Stretching, massage and drinking plenty of fluid, such as water, may be helpful in treating simple muscle cramps.[16] With exertional heat cramps due to electrolyte abnormalities (primarily sodium loss and not calcium, magnesium, and potassium), appropriate fluids and sufficient salt improves symptoms.[17]